1. Field of the Invention
There are many applications for small highly functionalized water soluble organic compounds. Such compounds find use as a stem for the preparation of non-ionic detergents, as buffers, or water solubilizing substituents. In the last situation, particular interest is their use in X-ray contrast media.
X-ray contrast media are involved for the visualization of extensive regions of the human body. The contrast reagents are required to have heavy atoms in high concentration to provide the desired opacity in the concerned region. Because of the requirement of high concentrations of these compounds in their use as contrast media, the presence of high proportions of heavier atoms, the desirability of water solubility, and the need for thermal and physiological stability, as well as low toxicity, there are heavy restraints on the type of compounds which may be employed. In addition to the aforementioned restraints, there are concerns with viscosity, osmotic pressure, synthesis, and the like.
Numerous iodinated compounds have been prepared for use as contrast media, but in each case, the compounds demonstrate one or more deficiencies. There has been, therefore, a continuing effort to develop new compounds which provide for better combinations of properties as contrast media.
A significant aspect of the development of a new contrast medium is the development of a process for the preparation of intermediates. The large amount of the compound which is used in an X-ray study makes simple, economic and efficient methods of preparation essential.
2. Description of the Prior Art
U.S. Pat. No. 3,701,771 describes triodobenzoyl sugar amines. Compounds which are presently commercially available include bis-3,5-diacetamido triiodobenzoate (diatrizoate), N,N'-di(1',3'-dihydroxypropyl-2') 5-L-lactoylamido triiodoisophthaldiamide (Iopamidol); and 3-acetamido-5-(N-methyl acetamido) triiodobenzoyl derivative of glucosamine (Metrizamide). Sovak, et al., Radiology 117:717 (1975) describe diiodotriglucosylbenzene. Weitl, et al., J. Med. Chem. 19 353 (1976) describe 2,4,6-triiodo-3-acetamido-5-(N-methyl carboxamido)phenyl .beta.-D-glucopyranoside as a contrast medium. In the Abstracts of the April ACS meeting (1979) is an Abstract by Ranganathan and Sovak, entitled "Synthesis of Carboxamido-triiodophenyl ethers of hexoses from nitroaromatics and their degradation into pentose derivatives." Co-pending U.S. patent application Ser. No. 034,099 now U.S. Pat. No. 4,243,653 describes non-glycosidyl carbohydrate ethers of triodo anilines. D-2-amino-2-deoxyerythritol and L-2-amino-2-deoxythreitol are described by Kiss and Sirokman, Helv. Chem. Acta 43, 334 (1960) and A. B. Foster et al, J. Chem. Soc. 1960, 2587, respectively.